Method and composition for cleaning and disinfecting contact lenses

ABSTRACT

Contact lenses are simultaneously cleaned and disinfected by contacting the lenses with an aqueous system containing an antimicrobial agent and a proteolytic enzyme for a period sufficient to clean and disinfect the lenses. The aqueous solutions have suitable osmotic values which do not substantially inhibit the activity of the antimicrobial agent.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation-in-part of U.S. applicationSer. No. 313,643 filed Feb. 21, 1989.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates to a method for cleaning and disinfectingcontact lenses and a composition for the same. More specifically, thepresent invention is directed to a method for simultaneously cleaningand disinfecting contact lenses by contacting the lenses with an aqueoussystem containing an antimicrobial agent and a proteolytic enzyme. Acomposition for simultaneously cleaning and disinfecting the lenses isalso provided.

[0004] 2. Description of Art

[0005] In the normal course of wearing contact lenses, tear film anddebris consisting of proteinaceous, oily, sebaceous, and related organicmatter have a tendency to deposit and build up on lens surfaces. As partof the routine care regimen, contact lenses must be cleaned to removethese tear film deposits and debris. If these deposits are not properlyremoved, both the wettability and optical clarity of the lenses issubstantially reduced causing discomfort for the wearer.

[0006] Further, contact lenses, especially those made from hydrophilicmaterials, must be continuously disinfected to kill any harmfulmicroorganisms that may be present or grow on the lenses. A number ofmethods for disinfecting contact lenses have been used such as the useof high temperatures, the use of oxidative chemicals, and the use ofantimicrobial agents. However, current disinfecting solutions do notexhibit significant cleaning ability for the removal of proteinaceousmaterial.

[0007] Conventionally, the cleaning of contact lenses is accomplishedwith one or both of two general classes of cleaners. Surfactantcleaners, generally known as “daily cleaners” because of theirrecommended daily use, are effective for the removal of mostcarbohydrate and lipid derived matter. However, they are not aseffective for the removal of proteinaceous matter such as lysozyme.Typically, proteolytic enzymes derived from plant, animal, and microbialsources are used to remove the proteinaceous deposits. These “enzyme”cleaners are recommended for weekly use and are conventionally employedby dissolving enzyme tablets in suitable aqueous solutions.

[0008] The process of cleaning and disinfecting contact lenses withenzyme cleaners (as well as daily cleaners) involves two steps. Thefirst step consists of the cleaning phase whereby lenses areconventionally soaked in an enzyme cleaning solution at ambienttemperature conditions, i.e., cold soaking for a period of up to 12hours, to achieve effective removal of proteinaceous deposits. At theconclusion of the cleaning step, the lenses are separately disinfected.Disinfection involves contacting the lenses with a solution containingeither an oxidative chemical or an antimicrobial agent at ambienttemperatures or exposing the lenses to elevated temperatures forspecified periods of time. The latter disinfection technique requiresspecific electrical disinfecting apparatus.

[0009] New methods have been developed which can remove proteinaceousmaterial from contact lenses while disinfecting the lenses. For example,U.S. Pat. No. 4,614,549 discloses a single-step method of cleaning anddisinfecting contact lenses in aqueous solutions of proteolytic enzymesat temperatures of between 60° C. and 100° C. This method requires theuse of electrical disinfecting apparatus and elevated temperatures. U.S.Patent Re. 32,672 discloses a method which immerses the lenses in asolution containing peroxide and a peroxide-active enzyme. However, thismethod requires an additional step for the neutralization of theresidual peroxide prior to inserting the lens into the eye.

[0010] In order to develop an improved simultaneous cleaning anddisinfecting method that does not require neutralization of anyoxidative chemical, proteolytic enzymes in tablet form were tested incombination with a disinfecting solution containing hexamethylenebiguanide polymers as the antimicrobial agent at ambient conditions.However, subsequent microbicidal efficacy studies revealed that theantimicrobial agent was rendered less effective for killing certainmicroorganisms during these initial studies.

[0011] However, it has now been discovered that the disinfecting abilityof antimicrobial agents, particularly at ambient temperatures, is mosteffective under conditions of suitable osmolality for the agentemployed. When the osmotic level of the solution is too high, theantimicrobial agents are rendered less effective for killing certainmicroorganisms.

[0012] Thus, according to this invention, proteolytic enzymes can beused in combination with antimicrobial agents to simultaneously cleanand disinfect contact lenses. Under ambient temperatures, thedisinfection has been found to be most effective at suitable osmoticconditions. The present invention provides a less complex and moreconvenient regimen for cleaning and disinfecting contact lenses withoutthe need for a separate neutralizing step or electrical disinfectingapparatus.

SUMMARY OF THE INVENTION

[0013] According to this invention, a method for simultaneously cleaningand disinfecting contact lenses is provided comprising contacting thelenses with an aqueous system containing an antimicrobial agent and aproteolytic enzyme for a time sufficient to clean and disinfect thelenses wherein the aqueous system has an osmotic value which does notsubstantially inhibit the activity of the antimicrobial agent.

[0014] Also provided is a composition for simultaneously cleaning anddisinfecting contact lenses containing an antimicrobial agent and aproteolytic enzyme wherein the final osmotic value of the composition isless than about 800 mOsm./kg. water.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention can be used with all contact lenses such asconventional hard, soft, rigid gas permeable, and silicone lenses but ispreferably employed with soft lenses such as those commonly referred toas hydrogel lenses prepared from monomers such ashydroxyethylmethacrylate, hydroxyethylmethyl methacrylate,vinylpyrrolidone, glycerol-methacrylate, methacrylic acid or acid estersan the like. Hydrogel lenses typically absorb significant amounts ofwater such as from 4 to 80 percent by weight.

[0016] The compositions employed herein for the cleaning anddisinfecting of contact lenses are composed of at least water, one ormore proteolytic enzymes, and one or more antimicrobial agents.Generally, these cleaning and disinfecting systems are prepared bymixing two components, the enzyme and a disinfecting solution containingthe antimicrobial agents. However, other methods of combining the activecomponents as well as off the shelf compositions containing all of theactive components are contemplated as being within the scope of thisinvention.

[0017] A wide variety of proteolytic enzymes are useful in the presentinvention such as those derived from plant, animal, and microbialsources. The separation and purification of these enzymes is well knownto those skilled in the art with many of these enzymes beingcommercially available. Moreover, it is anticipated that many of theenzymes can be prepared from new techniques being developed such asthose using recombinant DNA techniques and proteolytic enzymes preparedby these techniques are contemplated to be within the scope of thepresent invention.

[0018] The proteolytic enzymes used herein must have at least a partialcapability to hydrolyze peptide-amide bonds which reduces theproteinaceous material to smaller water-soluble subunits. Typically,these enzymes will exhibit some lipolytic, amylolytic or relatedactivities associated with the proteolytic activity and may be neutral,acidic or alkaline. In addition, separate lipases or carbohydrases maybe used in combination with the proteolytic enzymes.

[0019] Examples of suitable proteolytic enzymes include but are notlimited to pancreatin, trypsin, chymotrypsin, collagenase, papain,bromelain, aminopeptidase, Aspergillo peptidase, pronase E (from S.graseus) and dispose (from Bacillus polymyxa). The preferred group ofproteolytic enzymes are the microbial derived enzymes such as thosederived from Bacillus, Streptomyces, and Aspergillus microorganisms.Most preferred are the Bacillus derived alkaline proteases genericallycalled subtilisin enzymes. The subtilisin enzymes include bothsub-classes, subtilisin A and subtilisin B. Microbial derived enzymesare disclosed in U.S. Pat. No. 4,690,773 incorporated herein byreference.

[0020] The present invention employs an effective amount of enzyme toclean the lenses. An effective amount is that which removes asubstantial portion of the proteinaceous deposits which occur duringnormal wear in a reasonable time. The precise amount of enzyme requiredto make an effective cleaner will depend on several factors includingthe activity of the enzyme, the purity of the enzyme, the amount ofproteinaceous matter deposited on the lenses, the desired soakingperiod, the specific type of lenses, as well as other factors.

[0021] It should be appreciated to one skilled in the art, that theenzyme concentrations useful herein are adjusted depending upon the timeallowed for removing the proteinaceous material, the other components inthe solutions and the factors previously mentioned. Typically, when theenzyme is provided in solid form, it will be present in amounts fromabout 0.01 to about 200 milligrams.

[0022] Enzyme activity is generally pH dependent and there will be aparticular pH range in which any particular enzyme will function best.However, the determination of an optimum pH range can readily bedetermined by known techniques by those skilled in the art. It ispreferred that the enzyme be selected to have substantial activity at apH between about 6.5 and about 8.5.

[0023] The enzyme may be employed in liquid or solid form usually incombination with additional components. Preferably, the enzymes areprovided in solid form such as tablets or powders which are mixed withthe aqueous solutions prior to use.

[0024] Additional components may be added to or incorporated into theenzyme which do not substantially decrease the activity of the enzyme.For example, components such as effervescing agents, stabilizers,buffering agents, chelating and/or sequestering agents, coloring agents,tonicity adjusting agents, surfactants and the like can be employed. Inaddition, binders, lubricants, carriers, and other excipients normallyused in producing tablets may be incorporated into the enzyme whentablets are employed.

[0025] Examples of suitable buffering agents which may be incorporatedinto the enzyme include, but are not limited to, alkali metal salts suchas potassium or sodium carbonates, acetates, borates phosphates,citrates and hydroxides, and weak acids such as acetic and boric acids.Preferred buffering agents are alkali metal borates such as sodium orpotassium borates. Additionally, other pH adjusting agents may beemployed such as inorganic acids. For example, hydrogen chloride may beemployed in concentrations suitable for ophthalmic uses. Generally,buffering agents are present in amounts from about 0.01 to about 2.5percent by weight/volume (w/v).

[0026] Effervescing agents are typically employed when the enzyme isprovided in solid form. Examples of suitable effervescing agentsinclude, but are not limited to, tartaric or citric acid used incombination with a suitable alkali metal salt such as sodium carbonate.

[0027] The disinfecting solutions used with the present invention maycontain any of the above-mentioned enzyme components as well as othercomponents but typically will contain water, the antimicrobial agent,one or more of a suitable buffering agent, chelating and/or sequesteringagent, tonicity adjusting agent, the surfactant.

[0028] The tonicity adjusting agent which may be a component of thedisinfecting solution and may optically be incorporated into the enzymeis employed to adjust the osmotic value of the final cleaning anddisinfecting solution to more closely resemble that of human tears andto maintain a suitable level for optimum activity by the antimicrobialagent. Suitable tonicity adjusting agents include, but are not limitedto, sodium and potassium chloride, dextrose, calcium and magnesiumchloride, the buffering agents listed above are individually used inamounts ranging from about 0.01 to 2.5% (w/v) and preferably, from about0.5 to about 1.5% (w/v). Most preferably, the tonicity agent will beemployed in an amount to provide a final osmotic value of the cleaningand disinfecting solutions of less than about 800 millosmoles/kilogramwater (mOsm./kg. water).

[0029] Suitable surfactants can be either cationic, anionic, nonionic oramphoteric. Preferred surfactants are neutral or nonionic surfactantswhich may be present in amounts up to 5% (w/v). Examples of suitablesurfactants include, but are not limited to, polyethylene glycol estersof fatty acids, polyoxypropylene ethers of C₁₂-C₁₈ alkanes andpolyoxyethylene, polyoxypropylene block copolymers of ethylene diamine(i.e. poloxamine).

[0030] Examples of preferred chelating agents includeEthylenediaminetetraacetic acid (EDTA) and its salts (disodium) whichare normally employed in amounts from about 0.025 to about 2.0% (w/v).Other known chelating (or sequestering agents) such as certain polyvinylalcohols can also be employed.

[0031] The disinfecting solutions used with this invention will containa disinfecting amount of one or more antimicrobial agents which arecompatible with and do not precipitate in the presence of the enzymes.As used herein, antimicrobial agents are defined as non-oxidativeorganic chemicals which derive their antimicrobial activity through achemical or physicochemical interaction with the organisms. Suitableantimicrobial agents are polymeric quaternary ammonium salts used inophthalmic applications such as poly[(dimethyliminio)-2-butene-1,4-diylchloride], [4-tris(2-hydroxyethyl)ammonio]-2-butenyl-w-[tris(2-hydroxyethyl)ammonio]dichloride (chemicalregistry number 75345-27-6) generally available as polyquaternium 1^()from ONYX Corporation, benzalkonium halides, and biguanides such assalts of alexidine, alexidine free base, salts of chlorhexidine,hexamethylene biguanides and their polymers. The antimicrobial agentsused herein are preferrably employed in the absence ofmercury-containing compounds such as thimerosal. The salts of alexidineand chlorhexidine can be either organic or inorganic and are typicallygluconates, nitrates, acetates, phosphates, sulphates, halides and thelike. Preferred antimicrobial agents are the polymeric quaternaryammonium salts used in ephtalmic applications and the biguanides. Morepreferred are the biguanides with hexamethylene biguanides, theirpolymers and water-soluble salts being most preferred. Generally, thehexamethylene biguanide polymers, also referred to as polyaminopropylbiguanide (PAPB), have molecular weights of up to about 100,000. Suchcompounds are known and are disclosed in U.S. Pat. No. 4,758,595 whichis incorporated herein by reference.

[0032] A disinfecting amount of antimicrobial agent is an amount whichwill at least partially reduce the microorganism population in theformulations employed. Preferably, a disinfecting amount is that whichwill reduce the microbial burden by two log orders in four hours andmore preferably by one log order in one hour. Most preferably, adisinfecting amount is an amount which will eliminate the microbialburden on a contact lens when used in regimen for the recommendedsoaking time (FDA Chemical Disinfection Efficacy Test-July, 1985 ContactLens Solution Draft Guidelines). Typically, such agents are present inconcentrations ranging from about 0.00001 to about 0.5% (w/v), and morepreferably, from about 0.00003 to about 0.05% (w/v).

[0033] As mentioned above, it has been found that the antimicrobialagents at simulated commercial concentrations are rendered lesseffective in environments having high osmotic values, generally aboveabout 800 mOsm./kg. water at typical commercial concentrations(generally less than about 0.05% (w/v)). This is a particularlyimportant discovery since it is common in the industry to add bulkingagents to the active enzyme when used in tablet or powder form. Thesebulking agents usually increase the osmotic values of the cleaningsolutions, often significantly reducing the antimicrobial activity.Further, the various components discussed above, as well as others, mayalso raise the osmolality of the final formulation.

[0034] Moreover, it should also be understood that the particularosmotic value rendering any given antimicrobial agent ineffective willvary from agent to agent. The determination of the suitable osmoticrange for any particular antimicrobial agent can be easily determined byroutine experimentation by one skilled in the art. However, a preferredrange of osmotic values has been found to be less than about 800mOsm./kg. water and more preferable about 200 to about 600 mOsm./kg.water at antimicrobial agent concentrations of less than about 0.05%(w/v).

[0035] During practice of this invention, the enzyme formulation, eitherin solid or liquid form, is typically dissolved in a predeterminedamount of disinfecting solution which may be isotonic or hypotonic, toobtain a cleaning and disinfecting solution having the proper osmoticvalue. This solution is then contacted with lenses at ambienttemperatures for a sufficient time to clean and disinfect.

[0036] In a preferred embodiment of the invention, an enzyme tablet isdissolved in an aqueous disinfecting solution containing biguanide asthe antimicrobial agent in order to prepare the cleaning anddisinfecting solution. The lenses are then contacted with the cleaningand disinfecting solution, preferably by being immersed therein, andremain in contact with the solution for a sufficient period of time todisinfect the lenses. An effective amount of enzyme agent is used suchthat the time sufficient to disinfect will also be sufficient tosubstantially remove the proteinaceous deposits. Typically, the cleaningand disinfecting will take less than about 8 hours with about 1 to 4hours being preferred. Advantageously, the lenses can be removed fromthe solution and placed directly into the eye without the need for aseparate neutralizing step. Preferably, the lenses are rinsed with asuitable isotonic aqueous solution prior to insertion into the eye.

[0037] The following detailed examples are presented to illustrate thepresent invention.

EXAMPLE 1-36

[0038] In order to study the antimicrobial efficacy of the compositionsof the present invention, several aqueous solutions were prepared andevaluated for the log kill rate of Serratia marcescens.

[0039] Aqueous solutions were prepared having compositions whichsimulate commercial disinfecting solutions. All percentages indicatedthroughout these examples are in weight/volume. Each composition had0.85% boric acid, 0.09% sodium borate, 1.0% Tetronic® 1107 (a poloxaminesurfactant purchased from BASF Corporation), simulated commercialconcentrations of alexidine dihydrochloride, chlorhexidine gluconate,PAPB, polyquaternum 1^() (purchased from ONYX Corporation), andbenzalkonium chloride as he antimicrobial agent respectively and 0.005%of a proteolytic enzyme (subtilisin-A enzyme purchased from NOVOLaboratories, Inc.). The osmolality was varied using sodium chloride asthe tonicity adjusting agent. Two separate solutions were tested foreach composition. The compositions are shown in Table I.

[0040] The microbicidal activity of the above solutions were tested induplicate by exposing Serratia marcescens at about 1.0×10⁶ to about1.0×10⁷ colony forming units per milliliter (CFU/ml.) to 10 ml. of eachsolution at room temperature for 1 hour and 4 hour time intervals. Analiquot of each inoculated sample was removed at 1 and 4 hours anddiluted in a neutralizing broth (Dey-Engley) and plated withneutralizing agar. The agar plates were incubated for two days and platecounts were determined to calculate reduction in CFU/ml. for theorganism. The calculated log order reductions are shown in Table I.

[0041] As can be seen from Table I the log order reductions of thevarious antimicrobial agents tested were significantly reduced at highosmotic levels. TABLE I DISINFECTING MEASURED LOG SODIUM OSMOLALITYREDUCTION CHLORIDE (mOsm/kg S. MARCESCENS EXAMPLE DISINFECTING AGENT %(w/v) water) 1 Hour 4 Hours  1A Alexidine 1.0 ppm 0.20 200 2.6 >4.5  BAlexidine 1.0 ppm 0.20 200 2.6 >4.5  2A Alexidine 1.0 ppm 0.53 3021.2 >4.5  B Alexidine 1.0 ppm 0.53 302 1.2 >4.5  3A Alexidine 1.0 ppm0.85 404 0.5 >4.5  B Alexidine 1.0 ppm 0.85 404 0.6 >4.5  4A Alexidine1.0 ppm 1.15 500 0.2 3.4  B Alexidine 1.0 ppm 1.15 500 0.0 3.4  5AAlexidine 1.0 ppm 1.47 602 0.0 1.5  B Alexidine 1.0 ppm 1.47 602 0.0 1.6 6A Alexidine 1.0 ppm 2.09 800 0.0 1.1  B Alexidine 1.0 ppm 2.09 800 0.01.1  7A Chlorhex 100 ppm 0.20 202 >4.5 >4.5  B Chlorhex 100 ppm 0.20202 >4.5 >4.5  8A Chlorhex 100 ppm 0.53 306 >4.5 >4.5  B Chlorhex 100ppm 0.53 306 >4.5 >4.5  9A Chlorhex 100 ppm 0.85 402 2.0 >4.5  BChlorhex 100 ppm 0.85 402 2.0 >4.5 10A Chlorhex 100 ppm 1.15 5011.0 >4.5  B Chlorhex 100 ppm 1.15 501 1.4 >4.5 11A Chlorhex 100 ppm 1.47602 1.0 >4.5  B Chlorhex 100 ppm 1.47 602 1.0 >4.5 12A Chlorhex 100 ppm2.09 800 0.0 1.6  B Chlorhex 100 ppm 2.09 800 0.1 1.4 13A PAPB 1.0 ppm0.20 199 >4.5 >4.5  B PAPB 1.0 ppm 0.20 199 4.5 >4.5 14A PAPB 1.0 ppm0.53 301 4.2 >4.5  B PAPB 1.0 ppm 0.53 301 4.3 >4.5 15A PAPB 1.0 ppm0.85 402 3.0 >4.5  B PAPB 1.0 ppm 0.85 402 2.8 >4.5 16A PAPB 1.0 ppm1.15 501 2.7 >4.5  B PAPB 1.0 ppm 1.15 501 2.7 >4.5 17A PAPB 1.0 ppm1.47 601 1.9 >4.5  B PAPB 1.0 ppm 1.47 601 2.1 >4.5 18A PAPB 1.0 ppm2.09 801 0.3 >4.5  B PAPB 1.0 ppm 2.09 801 0.2 >4.5 19A Polyquaternium0.20 200 3.9 >4.5 1 100 ppm  B Polyquaternium 0.20 200 4.2 >4.5 1 100ppm 20A Polyquaternium 0.53 303 2.4 3.9 1 100 ppm  B Polyquaternium 0.53303 2.3 4.2 1 100 ppm 21A Polyquaternium 0.85 403 0.9 3.1 1 100 ppm  BPolyquaternium 0.85 403 0.9 3.0 1 100 ppm 22A Polyquaternium 1.15 5020.6 2.6 1 100 ppm  B Polyquaternium 1.15 502 0.5 2.4 1 100 ppm 23APolyquaternium 1.47 601 0.4 2.1 1 100 ppm  B Polyquaternium 1.47 601 0.42.1 1 100 ppm 24A Polyquaternium 2.09 802 0.4 1.4 1 100 ppm  BPolyquaternium 2.09 802 0.4 1.2 1 100 ppm 25A Benzalkonium 0.20200 >4.5 >4.5 Chloride 100 ppm  B Benzalkonium 0.20 200 >4.5 >4.5Chloride 100 ppm 26A Benzalkonium 0.53 304 >4.5 >4.5 Chloride 100 ppm  BBenzalkonium 0.53 304 >4.5 >4.5 Chloride 100 ppm 27A Benzalkonium 0.85404 >4.5 >4.5 Chloride 100 ppm  B Benzalkonium 0.85 404 >4.5 >4.5Chloride 100 ppm 28A Benzalkonium 1.15 499 >4.5 >4.5 Chloride 100 ppm  BBenzalkonium 1.15 499 >4.5 >4.5 Chloride 100 ppm 29A Benzalkonium 1.47598 >4.5 >4.5 Chloride 100 ppm  B Benzalkonium 1.47 598 >4.5 >4.5Chloride 100 ppm 30A Benzalkonium 2.09 801 2.7 >4.5 Chloride 200 ppm  BBenzalkonium 2.09 801 2.9 >4.5 Chloride 100 ppm 31A PAPB 0.5 ppm 0.20204 0.1 0.2  B PAPB 0.5 ppm 0.20 204 0.0 0.3 32A PAPB 0.5 ppm 0.53 3091.0 2.7  B PAPB 0.5 ppm 0.53 309 1.1 2.7 33A PAPB 0.5 ppm 0.85 402 0.11.5  B PAPB 0.5 ppm 0.85 402 0.2 1.5 34A PAPB 0.5 ppm 1.15 509 −0.1 0.2 B PAPB 0.5 ppm 1.15 509 −0.1 0.2 35A PAPB 0.5 ppm 1.47 607 0.0 −0.1  BPAPB 0.5 ppm 1.47 607 0.0 −0.1 36A PAPB 0.5 ppm 2.09 806 −0.1 0.0  BPAPB 0.5 ppm 2.09 806 0.0 0.0

EXAMPLE 37

[0042] In order to study the cleaning efficacy of the present invention,several solutions were prepared and evaluated for removal of lysozymedeposits from contact lenses.

[0043] The present light transmission through ten new Bausch & LombSoflens® (polymacon) Contact Lenses was read through a uv/visspectrophotometer at 500 and 280 nanometers (nm). An averagetransmission value was obtained (Tn) which was used below to calculatepercent protein removal. An aqueous solution was prepared containing0.7% NaCl, 0.22% sodium bicarbonate, 0.17% potassium chloride, 0.0005%calcium chloride and 0.15% lysozyme (3×crystallized from egg white).Five lenses were soaked in the lysozyme solution and heated for about 1hour at about 90° C. After heating, the lenses were removed, fingerrubbed and rinsed with isotonic saline solution to remove any nonboundlysozyme on the lenses. The percent light transmission was taken at 280and 500 nm (Td).

[0044] The lenses were then submerged in 10 ml. of an aqueous solutioncontaining 0.005% of subtilisin-A proteolytic enzyme (from NOVOLaboratories, Inc.) and alexidine di-hydrochloride (1 ppm) at osmoticvalues adjusted to 300 and 600 mOsm./kg. water. The lenses remained inthe solution for 1 hour at ambient temperature. The lenses were removed,rubbed and rinsed in an aqueous isotonic solution and soaked in theaqueous isotonic solution for an additional 15 minutes. The percentlight transmission was taken at 280 and 500 nm (Te).

[0045] The above transmission readings were placed into the followingequation at each reading (280 and 500 nm) to determine the percent oflysozyme removed:${\% \quad {protein}\quad {lysozyme}\quad {removed}} = \frac{\left( {{Tn} - {Td}} \right) - \left( {{Tn} - {Te}} \right)}{\left( {{Tn} - {Td}} \right)}$

[0046] The % protein removed at 500 nm (the visual range of light) andat 280 nm (specific for protein) is shown in Table II.

EXAMPLES 38-41

[0047] The procedure of Example 37 was repeated except thatchlorhexidine gluconate (100 ppm), PAPB (0.5 ppm), polyquaternium 1^()(100 ppm), and benzalkonium chloride (100 ppm) were substituted foralexidine dihydrochloride, respectively. The results are shown in TableII.

[0048] As can be seen from Table II, the present invention removesproteinaceous deposits from contact lenses. It should be mentioned, thatthe lysozyme deposition technique used herein results in much moresevere protein deposition that occurs during normal wear.

[0049] It is to be understood that the subject invention is not limitedby the above examples which have been provided merely to demonstrateoperability and which do not purport to be wholly definitive of thescope of this invention. The scope of this invention shall includeequivalent embodiments, modifications, and variations that fall withinthe scope of the attached claims. TABLE II CLEANING OSMOLALITY % PROTEINREMOVED % PROTEIN REMOVED PRESERVATIVE (mOam/kg. water) (500 nm) (280nm) 37. alexidine 1 300 93.4 49.5 2 76.8 35.3 3 75.0 33.3 4 92.5 42.4 557.4 35.8 Average 79.0 39.3 1 600 86.8 43.6 2 45.8 11.2 3 16.7 25.0 4 *33.3 5 70.3  2.9 Average 54.9 23.2 38. chlorhexidine 1 300 77.1 ** 225.0 ** 3 64.9 ** 4 78.9 ** 5 64.3 ** Average 62.0 ** 1 600 71.0 ** 253.8 ** 3 11.1 ** 4 79.3 ** 5 40.0 ** Average 51.0 ** 39. PAPB 1 30064.8 48.4 2 63.9 45.1 3 54.4 29.1 4 41.0 26.7 5 15.8 7.3 Average 48.031.3 1 600 50.0 32.9 2 68.0 27.8 3 31.2 31.1 4 66.7 66.4 5 66.0 45.9Average 56.4 40.8 40. polyquaternium 1 ® 1 300 95.9 71.2 2 70.0 42.2 385.8 56.7 4 50.9 21.5 5 34.1 26.2 Average 67.3 43.6 1 600 87.5 47.2 275.0 45.2 3 89.5 27.1 4 90.2 60.7 5 88.9 30.9 Average 86.2 42.2 41.benzalkonium chloride 1 300 17.4 39.5 2 37.5 27.1 3 46.2 37.2 4 44.027.2 5 48.0 35.4 Average 38.6 33.3 1 600 50.0 44.1 2 36.4 39.8 3 59.121.4 4  8.4 20.6 5 59.4 29.8 Average 42.7 31.1

What is claimed:
 1. A method for simultaneously cleaning anddisinfecting contact lenses comprising contacting the lenses with anaqueous system containing an antimicrobial agent selected from the groupconsisting of polymeric quaternary ammonium salts used in ophthalmicapplications, benzalkonium halides, and biguanides and a proteolyticenzyme for a time sufficient to clean and disinfect the lenses andwherein the osmotic value of said aqueous system does not substantiallyinhibit the activity of said antimicrobial agent.
 2. The method of claim1 wherein said antimicrobial agent and said proteolytic enzyme are in anaqueous solution.
 3. The method of claim 1 wherein said antimicrobialagents are used in the absence of thimerosal.
 4. The method of claim 1wherein said antimicrobial agent and said proteolytic enzyme arecontacted with the lenses at ambient temperatures.
 5. The method ofclaim 1 wherein said aqueous solution contains a tonicity adjustingagent.
 6. The method of claim 1 wherein the osmotic value is less thanabout 800 mOsm./kg. water.
 7. The method of claim 1 wherein saidantimicrobial agent is selected from the group consisting of polymericquaternary ammonium salts used in ophthalmic applications andbiguanides.
 8. The method of claim 7 wherein said antimicrobial agent isa biguanide.
 9. The method of claim 8 wherein said biguanide ishexamethylene biguanide polymer having molecular weights of up to about100,000.
 10. The method of claim 9 wherein said osmotic value is fromabout 200 to about 600 mOsm./kg. water.
 11. The method of claim 1wherein said proteolytic enzyme is in a powder or tablet form and isdissolved in a disinfecting solution containing water and saidantimicrobial agent to prepare said aqueous system.
 12. The method ofclaim 1 wherein said proteolytic enzyme is a subtilisin enzyme.
 13. Themethod of claim 4 wherein said aqueous solution additionally contains abuffering agent.
 14. The method of claim 4 wherein said aqueous solutionadditionally contains a surfactant.
 15. A method of simultaneouslycleaning and disinfecting contact lenses comprising the steps of:dissolving a proteolytic enzyme in a disinfecting solution containing,as the antimicrobial agent, from about 0.00001 to about 0.5 percent byweight/volume of a non-oxidative chemical selected from the groupconsisting of polymeric quaternary ammonium salts used in ophthalmicapplications, benzalkonium halides, and biguanides and from about 0.01to about 2.5 percent by weight/volume of a buffering agent and whereinsaid solution has a final osmotic value of less than about 800 mOsm./kg.water, and contacting said lenses with said solution for a period oftime sufficient to clean and disinfect said lenses.
 16. An improvedmethod for simultaneously cleaning and disinfecting contact lenses withproteolytic enzymes and antimicrobial agents in the absence ofthimerosal, the improvement comprising contacting the lenses with anaqueous system containing said enzyme and said antimicrobial agent isselected from the group consisting of polymeric quaternary ammoniumsalts used in ophthalmic applications, benzalkonium halides, andbiguanides, and maintaining the osmotic value of the system at a levelwhich does not substantially inhibit the activity of the antimicrobialagent.
 17. The method of claim 16 wherein said osmotic value is lessthan about 800 mOsm./kg. water.
 18. A composition for simultaneouslycleaning and disinfecting contact lenses said composition comprisingwater, a disinfecting amount of an antimicrobial agent selected from thegroup consisting of polymeric quaternary ammonium salts used inophthalmic applications, and biguanides and an effective amount of aproteolytic enzyme, wherein the final osmotic value of the compositionis less than about 800 mOsm./kg. water.
 19. The composition of claim 18wherein said composition is prepared by mixing said proteolytic enzymein a disinfecting solution containing said antimicrobial agent.
 20. Thecomposition of claim 19 wherein said antimicrobial agent is present inan amount ranging from about 0.00001 to about 0.5 percent byweight/volume.
 21. The composition of claim 20 wherein said proteolyticenzyme is in tablet or powder form.
 22. The composition of claim 21wherein a tonicity adjusting agent is present.
 23. The composition ofclaim 22 wherein said proteolytic enzyme is a subtilisin enzyme.
 24. Thecomposition of claim 20 wherein said antimicrobial agent is a biguanide.25. The composition of claim 24 wherein said biguanide is a polymer ofhexamethylene biguanide.
 26. The composition of claim 16 wherein asurfactant is present.
 27. The composition of claim 16 wherein abuffering agent is present.
 28. An aqueous composition for cleaning anddisinfecting contact lenses, said composition having a pH of about 6.5to about 8.5 and comprising about 0.00003 to about 0.05 percent byweight/volume of a hexamethylene biguanide polymer, an effective amountof a proteolytic enzyme, and wherein the final osmotic value of saidcomposition is less than about 800 mOsm./kg. water.